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Effect of tibolone pretreatment on kinases and phosphatases that regulate the expression and phosphorylation of Tau in the hippocampus of rats exposed to ozone

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Neural Regeneration Research 2018年第3期13卷 440-448页

作者： Rodolfo Pinto-Almazán Julia J. Segura-Uribe marvin A. soriano-ursúa Eunice D. Farfán-García Juan M. Gallardo Christian Guerra-Araiza Unidad de Investigación Hospital Regional de Alta Especialidad Ixtapaluca Carretera Federal México-Puebla km 34.5 C.P. 56530. Ixtapaluca State of Mexico Mexico Institute for the Developing Mind Children's Hospital Los Angeles Los Angeles CA USA Department of Pediatrics Keck School of Medicine University of Southern California Los Angeles CA USA Unidad de Investigación Médica en Enfermedades Neurológicas Hospital de Especialidades Centro Médico Nacional Siglo XXI Instituto Mexicano del Seguro Social Av. Cuauhtémoc 330 Col. Doctores. C. P. 06720. Mexico City Mexico Escuela Superior de Medicina Instituto Politécnico Nacional Plan de San Luis y Diaz Mirón Col. Casco de Santo Tomis. C. P. 11340. Mexico City Mexico Unidad de Investigación Médica en Enfermedades Nefrológicas Hospital de Especialidades Centro Médico Nacional Siglo XXI Instituto Mexicano del Seguro Social Av. Cuauhtémoc 330 Col. Doctores. C. P. 06720. Mexico City Mexico Unidad de Investigación Médica en Farmacologia Hospital de Especialidades Centro Médico Nacional Siglo XXI Instituto Mexicano del Seguro Social Av. Cuauhtémoc 330 Col. Doctores. C. P. 06720. Mexico City Mexico

Oxidative stress （OS） is a key process in the development of many neurodegenerative diseases, memory disorders, and other pathological processes related to aging. Tibolone （TIB）, a synthetic hormone used as a treatment for menopausal ymptoms, decreases lipoperoxidation levels, prevents memory impairment and learning disability caused by ozone （O3） exposure. However, it is not clear if TIB could prevent the increase in phosphorylation induced by oxidative stress of the microtubule-associated protein Tau. In this study, the effects of TIB at different times of administration on the phosphorylation of Tau, the activation of glycogen synthase kinase-3β （GSK3β）, and the inactivation of Akt and phosphatases PP2A and PTEN induced by O3 exposure were assessed in adult male Wistar rats. Rats were divided into 10 groups： control group （ozone-free air plus vehicle [C]）, control ＋ TIB group （ozone-free air plus TIB 1 mg/kg [C ＋ TIB]）; 7,15, 30, and 60 days of ozone exposure groups [O3] and 7, 15, 30, and 60 days of TIB 1 mg/kg before ozone exposure groups [O3 ＋ TIB]. The effects of O3 exposure and TIB administration were assessed by western blot analysis of total and phosphorylated Tau, GSK3β, Akt, PP2A, and PTEN proteins and oxidative stress marker nitrotyrosine, and superoxide dismutase activity and lipid peroxidation of malondialdehyde by two different spectrophotometric methods （Marklund and TBARS, respectively）. We observed that O3 exposure increases Tau phosphorylation, which is correlated with decreased PP2A and PTEN protein levels, diminished Akt protein levels, and increased GSK3β protein levels in the hippocampus of adult male rats. The effects of O3 exposure were prevented by the long-term treatment （over 15 days） with TIB. Malondialdehyde and nitrotyrosine levels increased from 15 to 60 days of exposure to O3 in comparison to C group, and superoxide dismutase activity decreased. Furthermore, TIB administration limited the changes induced by O3 exposure. Our results

关键词： tibolone oxidative stress ozone exposure Tau GSK3 hippocampus neuroprotection

Polyphenols as potential enhancers of stem cell therapy against neurodegeneration

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Neural Regeneration Research 2022年第10期17卷 2093-2101页

作者： Diana Rodríguez-Vera Antonio Abad-García Nancy Vargas-Mendoza Rodolfo Pinto-Almazán Eunice D.Farfán-García José A.Morales-González marvin A.soriano-ursúa Sección de Estudios de Posgrado e Investigación.Escuela Superior de Medicina Instituto Politécnico NacionalMéxico CityMéxico Unidad de Investigación Hospital Regional de Alta Especialidad IxtapalucaCarretera Federal México-Puebla km 34.5State of MéxicoMéxico

The potential of polyphenols for treating chronic-degenerative diseases(particularly neurodegenerative diseases)is ***,the selection of the best polyphenol for each treatment,the mechanisms by which they act,and their efficacy are frequently *** this review,the basics and the advances in the field,as well as suggestions for using natural and synthetic polyphenols alone or in a combinatorial strategy with stem cell assays,are compiled and ***,stem cells exhibit several responses when polyphenols are added to their environment,which could provide us with knowledge for advancing the elucidation of the origin of *** also,polyphenols are being included in the innovative strategies of novel therapies for treating neurodegenerative diseases as well as metabolic diseases related to *** this regard,flavonoid compounds are suggested as the best natural polyphenols due to their several mechanisms for acting in ameliorative effects;but increasing reports are involving other *** if some facts limiting bioactivity prevent them from conventional use,some natural polyphenols and derivatives hold the promise for being improved compounds,judged by their induced *** current results suggest polyphenols as enhancers of stem cell therapy against the targeted diseases.

关键词： Alzheimer’s disease chronic degenerative diseases combinatorial therapy metabolism neurodegenerative diseases neuronal damage neuroprotection Parkinson’s disease polyphenols stem cell assays

More than boric acid:Increasing relevance of boron in medicine

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World Journal of Translational Medicine 2018年第1期7卷 1-4页

作者： Eunice D Farfán-García Emily L Castillo-García marvin a soriano-ursúa Department of Physiology Escuela Superior de Medicina Instituto Politécnico Nacional

Although boron has been a chemical element of interest since the ancient times,only a few boron-containing compounds(BCCs)had been used for medicinal purposes before the 21^(st) *** these,only boric acid has been explored in multiple therapeutic ***,it is common to extrapolate from boric acid to all BCCs,supposing a similar biological ***,boric acid is just one of dozens of BCCs in nature and thousands available from chemical ***,there is a boom in research on new BCCs as potential tools in the prevention,diagnosis and therapy of human *** herein discuss the new role of BCCs in drug development,with emphasis on the compounds for which a mechanism of action has been proposed or *** of data gathered in recent years,BCCs have expanded beyond the well-known fields of antimicrobial and antineoplastic agents,now being explored for their possible use as enzyme inhibitors,regulators of protein expression and modulators of the immune response,as well as in *** suggest that translational medicine can accelerate the medicinal applications of BCCs,which is especially important for the human diseases that are generating a high global burden.

关键词： Boron Diagnosis Drug development Drug targets Immunological processes

Global longitudinal strain is superior to ejection fraction for detecting myocardial dysfunction in end-stage renal disease with hyperparathyroidism

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World Journal of Cardiology 2022年第4期14卷 239-249页

作者： Maria Fernanda Carrasco-Ruiz Antonio Ruiz-Rivera marvin a soriano-ursúa Carlos Martinez-Hernandez Leticia Manuel-Apolinar Carmen Castillo-Hernandez Gustavo Guevara-Balcazar Eunice D Farfán-García Ana Mejia-Ruiz Ivan Rubio-Gayosso Teresa Perez-Capistran Department of Physiology Escuela Superior de MedicinaInstituto Politécnico NacionalCiudad de México 11340Mexico Department of Cardiology Instituto Mexicano del Seguro SocialCiudad de México 06720Mexico Endocrine Research Unit Instituto Mexicano del Seguro SocialCiudad de México 06720Mexico Department of Cardiovascular Pharmacology Instituto Politécnico NacionalCiudad de México 11340Mexico Department of Biochemistry Escuela Superior de MedicinaInstituto Politécnico NacionalCiudad de México 11340Mexico Education Research Comisión Nacional Para la Mejora Continua de la EducaciónCiudad de México 03900Mexico Postgraduate Studies and Research Section Escuela Superior de MedicinaInstituto Politécnico NacionalCiudad de México 11340Mexico Department of Physiology Instituto Politécnico NacionalMexico City 11340Ciudad de MéxicoMexico

BACKGROUND The estimation of left ventricular ejection fraction(LVEF)by 2D echocardiography(2D-ECHO)is the most used tool to assess LV systolic function(LVSF).Global longitudinal strain(GLS)has recently been suggested as a superior method for several *** study explored the association and prevalence of LV systolic dysfunction(LVSD)by using these methods in patients with end-stage renal disease(ESRD)and severe hyperparathyroidism(SHPTH);both associated with cardiovascular events(CEs).AIM To evaluate the myocardial function in patients with ESRD and SHPTH by using the GLS and LVEF measured through conventional *** In 62 patients with ESRD and SHPTH,asymptomatic,and without a history of CEs,LVSF was evaluated by 2D-ECHO,obtaining the EF,by the Simpson biplane method,and GLS by speckle *** The total patients with ESRD had a preserved LVEF(>50%)but abnormal GLS(<13.55%).Additionally,multivariate analysis showed an independent association of GLS and serum parathyroid hormone(PTH),LV mass index,and ***,PTH was independently associated with lateral e'wave and tricuspid regurgitation *** In patients with SHPTH linked to ESRD,the use of GLS by 2D-ECHO is a more sensitive tool than LVEF for detecting LVSD.

关键词： Left ventricular hypertrophy Systolic dysfunction Global longitudinal strain End-stage renal disease Parathormone

Scope of translational medicine in developing boroncontaining compounds for therapeutics

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World Journal of Translational Medicine 2017年第1期6卷 1-9页

作者： Ana Karen García-ávila Eunice Dalet Farfán-García Juan Alberto Guevara-Salazar José Guadalupe Trujillo-Ferrara marvin Antonio soriano-ursúa Department of Biochemistry and Section of Post Graduate Studies and Research Escuela Superior de MedicinaInstituto Politécnico Nacional Department of Physiology and Section of Post Graduate Studies and Research Escuela Superior de MedicinaInstituto Politécnico Nacional

The ubiquitousness of naturally occurring boron-containing compounds(BCCs) has led to their constant contact with ***,many synthetic BCCs have been elaborated for a broad spectrum of purposes,especially boric,boronic and borinic *** BCCs were once employed primarily as antiseptics and later as antibiotics,they have become an increasingly relevant therapeutic ***,this potential of BCCs has been drastically limited due to some unfortunate intra-hospital accidents in the 1940 s and 1950 *** increasing use of BCCs as insecticides,antimicrobials,and other agents is providing new insights into their role in the physiology of several living species and in the pathophysiology of *** is becoming clear that BCCs act through a wide range of mechanisms,as do their corresponding boron-free *** comparing BCCs and similar boron-free compounds,in many cases the former show advantages in the medical *** current minireview focuses on how BCCs have been developed by means of translational medicine,a process connecting biomedical research with clinical *** process of discovery is currently in an exponential stage.

关键词： Boron Boron-containing compounds Drug development Toxicity Medicinal chemistry Pharmacology

Hepatoprotective effect of Geranium schiedeanum against ethanol toxicity during liver regeneration

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World Journal of Gastroenterology 2015年第25期21卷 7718-7729页

作者： Eduardo Madrigal-Santillán Mirandeli Bautista Juan A Gayosso-De-Lucio Yadira Reyes-Rosales Araceli Posadas-Mondragón ángel Morales-González marvin a soriano-ursúa Jazmín García-Machorro Eduardo Madrigal-Bujaidar Iselaálvarez-González JoséA Morales-González Laboratorio de Medicina de Conservación Escuela Superior de MedicinaInstituto Politécnico NacionalPlan de San Luis y Díaz MirónMéxico DF 11340México área Académica de Farmacia ICSaUniversidad Autónoma del Estado de HidalgoPachuca de Sotoestado de HidalgoCP 42000México Escuela Superior de Cómputo Instituto Politécnico NacionalAv.Juan de Dios Bátiz s/n esquina Miguel Othón de MendizabalUnidad Profesional Adolfo López Mateos Departamento de Fisiología Escuela Superior de MedicinaInstituto Politécnico NacionalPlan de San Luis y Díaz MirónColonia Casco de Santo TomasDel.Miguel HidalgoMéxico DF 11340México Laboratorio de Genética Escuela Nacional de Ciencias BiológicasInstituto Politécnico NacionalAv.Wilfrido MassieuUnidad A.López MateosZacatencoMéxico DF 07700México

AIM: To evaluate the effect of an extract of Geranium schiedeanum(Gs) as a hepatoprotective agent against ethanol(Et OH)-induced toxicity in rats. METHODS: Male Wistar rats weighing 200-230 g were subjected to a 70% partial hepatectomy(PH); they were then divided into three groups(groups 1-3). During the experiment, animals in group 1 drank only water. The other two groups(2-3) drank an aqueous solution of Et OH(40%, v/v). Additionally, rats in group 3 received a Gs extract daily at a dose of 300 mg/kg body weight intragastically. Subsequently, to identify markers of liver damage in serum, alanine aminotransferase, aspartate aminotransferase, albumin and bilirubin were measured by colorimetric methods. Glucose, triglyceride and cholesterol concentrations were also determined. In addition, oxidative damage was estimated by measuring lipid peroxidation [using thiobarbituric-acid reactive substances(TBARS)] in both plasma and the liver and by measuring the total concentration of antioxidants in serum and the total antioxidant capacity in the liver. In addition, a liver mass gain assessment, total DNA analysis and a morpho-histological analysis of the liver from animals in all three groups were performed and compared. Finally, the number of deaths observed in the three groups was ***: Administration of the Geranium shiedeanum extract significantly reduced the unfavorable effect of ethanol on liver regeneration(restitution liver mass: PHEt OH group 60.68% vs PH-Gs-Et OH group 69.22%). This finding was congruent with the reduced levels of hepatic enzymes and the sustained or increased levels of albumin and decreased bilirubin in serum. The extract also modified the metabolic processes that regulate glucose and lipid levels, as observed from the serum measurements. Lower antioxidant levels and the liver damage induced by Et OH administration appeared to be mitigated by the extract, as observed from the TBARs(PH-Et OH group 200.14 mmol/mg vs PH-Gs-Et OH group 5

关键词： Geranium schiedeanum Liver regeneration Ethanol Free radicals Nuclear factor erythroid-2-relatedfactor 2

Insights into the structural biology of G-protein coupled receptors impacts drug design for central nervous system neurodegenerative processes

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Neural Regeneration Research 2013年第24期8卷 2290-2302页

作者： Farfán-García Eunice Dalet Trujillo-Ferrara José Guadalupe Castillo-Hernández María del Carmen Guerra-Araiza Christian Humberto soriano-ursúa marvin Antonio Escuela Superior de Medicina Instituto Politécnico Nacional. Plan de San Luis y Díaz Mirón s/n Col. Casco de Santo Tomas

In the last few years, there have been important new insights into the structural biology of G-protein coupled receptors. It is now known that allosteric binding sites are involved in the affinity and selec- tivity of ligands for G-protein coupled receptors, and that signaling by these receptors involves both G-protein dependent and independent pathways. The present review outlines the physiological and pharmacological implications of this perspective for the design of new drugs to treat disorders of the central nervous system. Specifically, new possibilities are explored in relation to allosteric and or- thosteric binding sites on dopamine receptors for the treatment of Parkinson＇s disease, and on muscarinic receptors for Alzheimer＇s disease. Future research can seek to identify ligands that can bind to more than one site on the same receptor, or simultaneously bind to two receptors and form a dimer. For example, the design of bivalent drugs that can reach homo/hetero-dimers of D2 dopa- mine receptor holds promise as a relevant therapeutic strategy for Parkinson＇s disease. Regarding the treatment of Alzheimer＇s disease, the design of dualsteric ligands for mono-oligomeric mus- carinic receptors could increase therapeutic effectiveness by generating potent compounds that could activate more than one signaling pathway.

关键词： neural regeneration G-Protein coupled receptors structural biology drug design neurodegenera-tive disorders , oligomedzation biased signaling Parkinson's disease Alzheimer's disease dopa-mine receptors muscarinic receptors grants-supported paper neuroregeneration

Temporal allocation of metabolic tolerance in the body of beet armyworm in response to three gossypol-cotton cultivars

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Science China(Life Sciences) 2009年第12期52卷 1140-1147页

作者： marvin K HARRIS Department of Entomology Texas A&M University of USA

The nutrient composition and enzyme activities in larvae of the beet armyworm, Spodoptera exigua (Hbner), fed on high, medium or low gossypol cotton cultivars were examined at different time intervals. Significantly lower free fatty acid was observed in larvae fed for 6 h on high gossypol 'M9101' compared to larvae fed on the low (ZMS13) and intermediate (HZ401) gossypol cultivars. Significantly higher trypsin activity was observed in larvae fed on high gossypol 'M9101' for 24 h compared to those fed for 1, 4 and 6 h. Significantly higher catalase and total superoxide dismutase enzyme activities were observed in larvae of S. exigua fed on high gossypol 'M9101' compared with low gossypol cultivars 'ZMS13' and 'HZ401' for 1, 4, 6 and 24 h. However, significantly lower carboxylesterase and acetylcholinesterase enzyme activities were found in larvae fed on high gossypol 'M9101' compared with the other cultivars for 1, 4, 6 and 24 h. The interaction between cotton variety and beet armyworm infestation time significantly affected the carboxylesterase enzyme activity in S. exigua. The characterization of the effects of plant allelochemicals on herbivorous larvae is important for aiding understanding of plant-insect interaction as well as in devising solutions to pest problems by breeding plant resistance, identifying metabolic targets for insecticide development, etc.

关键词： Spodoptera exigua gossypol free fatty acid detoxification enzyme acetylcholinesterase total superoxide dismutase

Data-driven prediction of plate velocities and plate deformation of explosive reactive armor

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Defence Technology（防务技术） 2022年第12期18卷 2141-2149页

作者： marvin Becker Andreas Klavzar Thomas Wolf Melissa Renck Institute of Saint-Louis 5 Rue du Général Cassagnou68330Saint LouisCedexFrance Ecole Centrale de Lille CitéScientifique59651Villeneuve d'AscqCedexFrance

Explosive reactive armor(ERA)is currently being actively developed as a protective system for mobile devices against ballistic threats such as kinetic energy penetrators and shaped-charge *** mobility,the aim is to design a protection system with a minimal amount of required *** efficiency of an ERA is sensitive to the impact position and the timing of the ***,different designs have to be tested for several impact scenarios to identify the best *** analytical models are not predicting the behavior of the ERA accurately enough and experiments,as well as numerical simulations,are too time-consuming,a data-driven model to estimate the displacements and deformation of plates of an ERA system is proposed *** ground truth for the artificial neural network(ANN)is numerical simulation results that are validated with *** ANN approximates the plate positions for different materials,plate sizes,and detonation point positions with sufficient accuracy in *** a future investigation,the results from the model can be used to estimate the interaction of the ERA with a given ***,a measure for the effectiveness of an ERA can be ***,an optimal ERA can be designed and analyzed for any possible impact scenario in negligible time.

关键词： Artificial neural network Explosive reactive armor Finite element simulation Particle simulation Flash X-ray